Verapamil abolishes exercise-induced regional contractile dysfunction in dogs

The effects of the Ca++-antagonist verapamil on hemodynamic and regional myocardial functional parameters were studied in a canine model of exercise-induced myocardial dysfunction which mimics exercise-induced angina pectoris. Six dogs, trained to submit to five treadmill exercise cycles, each consisting of 4 min of running and 11 min of recovery, were chronically instrumented with a microtip manometer in the left ventricle, two pairs of crystals for sonomicrometry, a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Control experiments with coronary stenosis clarified the reproducibility of exercise-induced regional contractile dysfunction and recovery of function in the intervening resting periods. In each individual dog, the same degree of stenosis was used in the subsequent experiments with verapamil. After two control runs which exhibited regional contractile dysfunction of comparable magnitude, verapamil was administered intravenously at a dosage of 0.3 mg/kg over a period of 5 min. Verapamil induced an increase in heart rate at rest due to sympathetic counterregulation secondary to a reduction of systolic and diastolic blood pressure. The exercise-induced increases in heart rate and rate-pressure product were reduced after verapamil, but the exercise-induced increase in left ventricular dp/dtmax was not significantly diminished. The hemodynamic changes led to a marked improvement of regional function during exercise in the area perfused by the stenosed coronary artery. In a study using identical experimental conditions, the Ca++-antagonist bepridil at a dosage of 2 mg/kg/5 min abolished the exercise-induced regional contractile dysfunction to a similar extent as verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)